Response to Tsuda et al. "demonstrating the undermining of science and health policy after the Fukushima nuclear accident by applying the toolkit for detecting misused epidemiological methods".

BACKGROUND: The SHAMISEN (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) European project was conducted in 2015-2017 to review the lessons learned from the experience of past nuclear accidents and develop recommendations for preparedness and health surveillance of populations affected by a nuclear accident. Using a toolkit approach, Tsuda et al. recently published a critical review of the article by Cléro et al. derived from the SHAMISEN project on thyroid cancer screening after nuclear accident. MAIN BODY: We address the main points of criticism of our publication on the SHAMISEN European project. CONCLUSION: We disagree with some of the arguments and criticisms mentioned by Tsuda et al. We continue to support the conclusions and recommendations of the SHAMISEN consortium, including the recommendation not to launch a mass thyroid cancer screening after a nuclear accident, but rather to make it available (with appropriate information counselling) to those who request it.

Radiation detriment calculation methodology: summary of ICRP Publication 152.

Radiation detriment is a concept to quantify the burden of stochastic effects from exposure of the human population to low-dose and/or low-dose-rate ionising radiation. As part of a thorough review of the system of radiological protection, the International Commission on Radiological Protection (ICRP) has compiled a report on radiation detriment calculation methodology as Publication 152. It provides a historical review of the detriment calculation with details of the procedure used in ICRP Publication 103. A selected sensitivity analysis was conducted to identify the parameters and calculation conditions that can be major sources of variation and uncertainty. It has demonstrated that sex, age at exposure, dose and dose-rate effectiveness factor, dose assumption in the lifetime risk calculation, and lethality fraction have a substantial impact on the calculated values of radiation detriment. Discussions are also made on the issues to be addressed and possible ways for improvement toward the revision of general recommendations. These include update of the reference population data and cancer severity parameters, revision of cancer risk models, and better handling of the variation with sex and age. Finally, emphasis is placed on transparency and traceability of the calculation, along with the need to improve the way of expressing and communicating the detriment.

Cancer risk from chronic exposures to chemicals and radiation: a comparison of the toxicological reference value with the radiation detriment.

This article aims at comparing reference methods for the assessment of cancer risk from exposure to genotoxic carcinogen chemical substances and to ionizing radiation. For chemicals, cancer potency is expressed as a toxicological reference value (TRV) based on the most sensitive type of cancer generally observed in animal experiments of oral or inhalation exposure. A dose-response curve is established by modelling experimental data adjusted to apply to human exposure. This leads to a point of departure from which the TRV is derived as the slope of a linear extrapolation to zero dose. Human lifetime cancer risk can then be assessed as the product of dose by TRV and it is generally considered to be tolerable in a 10-6-10-4 range for the public in a normal situation. Radiation exposure is assessed as an effective dose corresponding to a weighted average of energy deposition in body organs. Cancer risk models were derived from the epidemiological follow-up of atomic bombing survivors. Considering a linear-no-threshold dose-risk relationship and average baseline risks, lifetime nominal risk coefficients were established for 13 types of cancers. Those are adjusted according to the severity of each cancer type and combined into an overall indicator denominated radiation detriment. Exposure to radiation is subject to dose limits proscribing unacceptable health detriment. The differences between chemical and radiological cancer risk assessments are discussed and concern data sources, extrapolation to low doses, definition of dose, considered health effects and level of conservatism. These differences should not be an insuperable impediment to the comparison of TRVs with radiation risk, thus opportunities exist to bring closer the two types of risk assessment.

Residential exposure to natural background radiation at birth and risk of childhood acute leukemia in France, 1990-2009.

BACKGROUND: The role of natural background radiation (NBR) in childhood acute leukemia (AL) remains unclear. Several large record based studies have recently reported heterogeneous results. Differences in exposure assessment timing may explain this heterogeneity. OBJECTIVES: In a previous ecological study we did not observe any association between childhood AL incidence in France and NBR exposure at the time of diagnosis. With the same methodology, the present study focused on NBR exposure at the time of birth. Based on data from the French national registry of childhood cancer, we analyzed all AL together, and lymphoblastic and myeloid AL, separately. METHODS: We included 6,059 childhood AL cases born and diagnosed in mainland France between 1990 and 2009. NBR levels in municipalities of residence at birth were estimated by cokriging models, using NBR measurements and precise geological data. The incidence rate ratio (IRR) per unit variation of exposure was estimated with Poisson regression models, with adjustment for socio-demographic indicators and ultraviolet radiation levels. NBR exposures were considered at the time of birth, and cumulatively from birth to diagnosis. We also estimated a total NBR dose to red-bone marrow (RBM). RESULTS: There was no evidence for an association between NBR exposure at birth and childhood AL incidence, neither overall (gamma radiation: IRR = 0.99 (0.94,1.05) per 50 nSv/h; radon: IRR = 0.97 (0.91,1.03) per 100 Bq/m3) nor for the main AL types. The conclusions were similar with the cumulative exposures, and the total RBM dose. CONCLUSIONS: The study was based on high quality incidence data, large numbers of AL cases, and validated models of NBR exposure assessment. In all, the results further support the hypothesis that NBR are not associated to childhood AL in France.

Lessons learned from Chernobyl and Fukushima on thyroid cancer screening and recommendations in case of a future nuclear accident.

Exposure of the thyroid gland to ionizing radiation at a young age is the main recognized risk factor for differentiated thyroid cancer. After the Chernobyl and Fukushima nuclear accidents, thyroid cancer screening was implemented mainly for children, leading to case over-diagnosis as seen in South Korea after the implementation of opportunistic screening (where subjects are recruited at healthcare sites). The aim of cancer screening is to reduce morbidity and mortality, but screening can also cause negative effects on health (with unnecessary treatment if over-diagnosis) and on quality of life. This paper from the SHAMISEN special issue (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) presents the principles of cancer screening, the lessons learned from thyroid cancer screening, as well as the knowledge on thyroid cancer incidence after exposure to iodine-131. The SHAMISEN Consortium recommends to envisage systematic health screening after a nuclear accident, only when appropriately justified, i.e. ensuring that screening will do more good than harm. Based on the experience of the Fukushima screening, the consortium does not recommend mass or population-based thyroid cancer screening, as the negative psychological and physical effects are likely to outweigh any possible benefit in affected populations; thyroid health monitoring should however be made available to persons who request it (regardless of whether they are at increased risk or not), accompanied with appropriate information and support.

Sensitivity analysis of parameters and methodological choices used in calculation of radiation detriment for solid cancer.

Purpose: Radiation detriment is a concept used by the International Commission on Radiological Protection (ICRP) to quantify the harmful health effects of radiation exposure in humans. The current approach of radiation detriment calculation has been defined in ICRP Publication 103 in 2007. It is determined from lifetime risk of cancer and heritable effects for a composite reference population, taking into account the severity of the disease in terms of lethality, quality of life and years of life lost. Many parameters are used in the calculations and the variation of these parameters can have effects on the cancer detriment, which needs to be investigated.Materials and methods: In this paper, we conducted a sensitivity analysis for examining the impact of 12 different parameters or methodological choices on the calculation of solid cancer detriment, such as the lifetime risk calculation method, survival curve, dose and dose-rate effectiveness factor (DDREF), age-at-exposure, sex, reference population, risk transfer model, latency, attained age, lethality, minimum quality of life factor and relative cancer-free life lost. Sensitivity calculations have been performed systematically for each of 10 solid cancer sites, by changing each one of the parameters in turn.Results: This sensitivity analysis demonstrated a large impact on estimated detriment from DDREF, age-at-exposure, sex and lethality, a noticeable impact of risk transfer model associated to variation of baseline rates, and a limited impact of risk calculation method, survival curve, latency, attained age, quality of life and relative years of life lost.Conclusion: These results could have implications for radiation protection standards, and they should help define priorities for future research in the field of low radiation dose and dose rate research. The present sensitivity analysis is part of a global effort of ICRP to review the bases of radiation detriment calculation and assess potential evolutions to improve the radiation protection system.

Ecological association between residential natural background radiation exposure and the incidence rate of childhood central nervous system tumors in France, 2000-2012.

BACKGROUND: High-dose ionizing radiation is an established risk factor for childhood central nervous system tumors (CNST) but the role of low doses remains debated. In particular, there are few studies of natural background radiation (NBR, gamma radiation and radon) and childhood CNST, and their results are inconclusive. OBJECTIVES: This study aimed to investigate the ecological association between NBR exposure and childhood CNST incidence in France, considering childhood CNST overall and by subgroups. METHODS: Incidence data were provided by the French national registry of childhood cancers, which has high completeness. We included 5471 childhood CNST cases registered over the period 2000-2012, and their municipality of residence at diagnosis was recorded. Municipality NBR exposures were estimated by cokriging models, using NBR measurements and additional geographic data. The incidence rate ratio (IRR) per unit variation of exposure was estimated with Poisson regression models. NBR exposures were considered at the time of diagnosis, and cumulatively from birth to diagnosis. In an exploratory analysis, the total brain dose due to NBR was used. RESULTS: Overall, there was no association between NBR exposure and childhood CNST incidence (IRR = 1.03 (0.98,1.09) per 50 nSv/h for gamma radiation, and IRR = 1.02 (0,96,1.07) per 100 Bq/m3 for radon). An association was suggested between pilocytic astrocytomas and gamma radiation (IRR = 1.12 (1.00,1.24) per 50 nSv/h) but not with radon (IRR = 1.07 (0.95,1.20) per 100 Bq/m3). Upward trends for this CNST subtype were also suggested with the cumulative exposures to gamma radiation and the total brain dose. NBR exposure was not associated with other CNST subgroups (ependymomas, embryonal tumors, and gliomas other than pilocytic astrocytomas). Adjustment for socio-demographic factors did not change the findings. CONCLUSIONS: Our study was based on high quality incidence data, large numbers of CNST cases, and validated models of NBR exposure assessment. Results suggest an association between gamma radiation, as a component of NBR, and pilocytic astrocytomas incidence in France.

History of radiation detriment and its calculation methodology used in ICRP Publication 103.

Over the past decades, the International Commission on Radiological Protection (ICRP) has used radiation detriment, which is a multidimensional concept to quantify the overall harm to health from stochastic effects of low-level radiation exposure of different parts of the body. Each tissue-specific detriment is determined from the nominal tissue-specific risk coefficient, weighted by the severity of the disease in terms of lethality, impact on quality of life and years of life lost. Total detriment is the sum of the detriments for separate tissues and organs. Tissue weighting factors for the calculation of effective dose are based on relative contributions of each tissue to the total detriment. Calculating radiation detriment is a complex process that requires information from various sources and judgements on how to achieve calculations. As such, it is important to document its calculation methodology. To improve the traceability of calculations and form a solid basis for future recommendations, the ICRP Task Group 102 on detriment calculation methodology was established in 2016. As part of its mission, the history of radiation detriment was reviewed, and the process of detriment calculation was detailed. This article summarises that work, aiming to clarify the methodology of detriment calculation currently used by ICRP.

The risk of cancer attributable to diagnostic medical radiation: Estimation for France in 2015.

Although medical ionizing radiation (IR) has clear clinical benefits, it is an established carcinogen. Our study estimates the number of new cancer cases in France in 2015 attributable to IR exposure from medical procedures. Exposures from external (X-rays, CT scans, interventional radiology) and internal (nuclear medicine) sources were considered. We used 2007 national frequencies of diagnostic examinations by sex and age to estimate the lifetime organ dose exposure adjusted for changes in the use of such procedures over time. The Biological Effects of Ionizing Radiation VII risk models were used to estimate the corresponding excess cancer risk, assuming an average latency period of 10 years. Additionally, we used cancer incidence data from the French Cancer Registries Network. Of the 346,000 estimated new cancer cases in adults in France in 2015, 2300 cases (940 among men and 1360 among women) were attributable to diagnostic IR, representing 0.7% of all new cancer cases (0.5% for men and 0.9% for women). The leading cancers attributable to medical IR were female breast (n = 560 cases), lung (n = 500 cases) and colon (n = 290 cases) cancers. Compared to other risk factors, the contribution of medical IR to the cancer burden is small, and the benefits largely outweigh its harms. However, some of these IR-associated cancer cases may be preventable through dose optimization of and enhanced justification for diagnostic examinations.

Cancers in France in 2015 attributable to occupational exposures.

BACKGROUND: Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking. OBJECTIVES: To estimate the number of new cancer cases attributable to occupational exposures, using a newly developed methodology and the most recent data, for a comprehensive set of occupational carcinogens in France in 2015. METHODS: Surveys among employees, the national labor force data, a cohort of agricultural workers, national monitoring of workers exposed to ionizing radiation and job-exposure matrix in France were used. The number and proportion of new cancer cases attributable to established occupational carcinogens (Group 1) was estimated using estimation of lifetime exposure and risk estimates from cohort studies. Cancer data were obtained from the French Cancer Registries Network. RESULTS: In France in 2015, an estimated 7905 new cancer cases, 7336 among men and 569 among women, were attributable to occupational exposures, representing 2.3% of all new cancer cases (3.9% and 0.4% among men and women respectively). Among men and women, lung cancer was impacted the most, followed by mesothelioma and bladder cancer in men, and by mesothelioma and ovary in women. These cancers contributed to 89% of the total cancers attributable to occupational carcinogens in men, and to 80% in women. The main contributing occupational agent was asbestos among men (45%) and women (60%). CONCLUSIONS: Currently, occupational exposures contribute to a substantial burden of cancer in France. Enhanced monitoring and implementation of protective labor policies could potentially prevent a large proportion of these cancers.

Quantitative health impact of indoor radon in France.

Radon is the second leading cause of lung cancer after smoking. Since the previous quantitative risk assessment of indoor radon conducted in France, input data have changed such as, estimates of indoor radon concentrations, lung cancer rates and the prevalence of tobacco consumption. The aim of this work was to update the risk assessment of lung cancer mortality attributable to indoor radon in France using recent risk models and data, improving the consideration of smoking, and providing results at a fine geographical scale. The data used were population data (2012), vital statistics on death from lung cancer (2008-2012), domestic radon exposure from a recent database that combines measurement results of indoor radon concentration and the geogenic radon potential map for France (2015), and smoking prevalence (2010). The risk model used was derived from a European epidemiological study, considering that lung cancer risk increased by 16% per 100 becquerels per cubic meter (Bq/m3) indoor radon concentration. The estimated number of lung cancer deaths attributable to indoor radon exposure is about 3000 (1000; 5000), which corresponds to about 10% of all lung cancer deaths each year in France. About 33% of lung cancer deaths attributable to radon are due to exposure levels above 100 Bq/m3. Considering the combined effect of tobacco and radon, the study shows that 75% of estimated radon-attributable lung cancer deaths occur among current smokers, 20% among ex-smokers and 5% among never-smokers. It is concluded that the results of this study, which are based on precise estimates of indoor radon concentrations at finest geographical scale, can serve as a basis for defining French policy against radon risk.

Is exposure to ionising radiation associated with childhood cardiac arrhythmia in the Russian territories contaminated by the Chernobyl fallout? A cross-sectional population-based study.

OBJECTIVE: To investigate childhood cardiac arrhythmia and chronic exposure to caesium-137 (137Cs) resulting from the Chernobyl accident. DESIGN: Prospective cross-sectional study using exposed/unexposed design conducted in the Bryansk region from May 2009 to May 2013 on children selected on the basis of 137Cs soil deposition: control territories ([137Cs]<37 kBq per square metre, where children were considered as unexposed) and contaminated territories ([137Cs]>555 kBq per square metre, where children were considered as exposed). SETTING: Russian territories affected by the Chernobyl fallout (Bryansk region). PARTICIPANTS: This cross-sectional study included 18 152 children aged 2-18 years and living in the Bryansk region (Russia). MAIN OUTCOME MEASURES: All children received three medical examinations (ECG, echocardiography and 137Cs whole-body activity measurement) and some of them were given with a 24-hour Holter monitoring and blood tests. RESULTS: Cardiac arrhythmia was diagnosed in 1172 children living in contaminated territories and 1354 children living in control territories. The crude prevalence estimated to 13.3% in contaminated territories was significantly lower than in control territories with 15.2% over the period 2009-2013 (P<0.001). Considering 137Cs whole-body burden as exposure, cardiac arrhythmia was found in 449 contaminated children and 2077 uncontaminated children, corresponding to an estimated crude prevalence of 14.5% and 14.2%, respectively, which does not differ significantly (P=0.74). Also, we investigated the association between territory, exposure to 137Cs and cardiac arrhythmia: the adjusted OR was not significant (0.90 with 95% CI 0.81 to 1.00; P=0.06) for the territory. For 137Cs whole-body burden, the ORs close to 1 did not reach statistical significance (P for trend=0.97). CONCLUSION: This study does not observe an association between cardiac arrhythmia and 137Cs deposition levels in the Bryansk region exposed to Chernobyl fallout. The suspected increase of cardiac arrhythmia in children exposed to Chernobyl fallout is not confirmed.

Impact of considering non-occupational radiation exposure on the association between occupational dose and solid cancer among French nuclear workers.

OBJECTIVES: The French nuclear worker cohort allows for the assessment of cancer risk associated with occupational radiation exposure, but workers are also exposed to medical and environmental radiation which can be of the same order of magnitude. This study aims to examine the impact of non-occupational radiation exposures on the dose-risk analysis between occupational radiation exposure and cancer mortality. METHODS: The cohort included workers employed before 1995 for at least one year by CEA, AREVA NC or EDF and badge-monitored for external radiation exposure. Monitoring results were used to calculate occupational individual doses. Scenarios of work-related X-ray and environmental exposures were simulated. Poisson regression was used to quantify associations between occupational exposure and cancer mortality adjusting for non-occupational radiation exposure. RESULTS: The mean cumulative dose of external occupational radiation was 18.4 mSv among 59 004 workers. Depending on the hypotheses made, the mean cumulative work-related X-ray dose varied between 3.1 and 9.2 mSv and the mean cumulative environmental dose was around 130 mSv. The unadjusted excess relative rate of cancer per Sievert (ERR/Sv) was 0.34 (90% CI -0.44 to 1.24). Adjusting for environmental radiation exposure did not substantially modify this risk coefficient, but it was attenuated by medical exposure (ERR/Sv point estimate between 0.15 and 0.23). CONCLUSIONS: Occupational radiation risk estimates were lower when adjusted for work-related X-ray exposures. Environmental exposures had a very slight impact on the occupational exposure risk estimates. In any scenario of non-occupational exposure considered, a positive but insignificant excess cancer risk associated with occupational exposure was observed.

FOXE1 Polymorphism Interacts with Dietary Iodine Intake in Differentiated Thyroid Cancer Risk in the Cuban Population.

BACKGROUND: The incidence of differentiated thyroid cancer (DTC) is low in Cuba, and the contribution of dietary factors to DTC in this population has not been investigated so far. The aim of this study was to evaluate the relationship between dietary iodine intake and DTC with regard to the interaction with environmental factors or some common single nucleotide polymorphisms (SNPs), based on a case-control study carried out in Cuba. METHODS: A total of 203 cases and 212 controls from the general population were interviewed face-to-face using the dietary intake questionnaire and the photo booklet from the E3N cohort. A specific food composition table was constructed for this study. For each parameter studied, the odds ratio (OR) was stratified on age group and sex, and further adjusted for dietary energy, smoking status, ethnic group, level of education, number of pregnancies, and body surface area. RESULTS: The risk of DTC was significantly reduced with increasing consumption of fish (p = 0.04), but no association between total dietary iodine intake and DTC risk was evident (p = 0.7). This lack of significant association was true whatever the age, the smoking status, the dietary selenium intake, and the ethnicity (p > 0.05). DTC risk was positively and strongly associated with the number of copies in the minor allele (A) for SNP rs965513 near FOXE1 among people who consumed less iodine than the median (p = 0.005). CONCLUSION: Overall, the majority of the studied population had an optimal dietary iodine intake. DTC risk was inversely associated with high fish consumption. Furthermore, DTC risk was positively associated with the number of copies in the minor allele (A) of rs965513 among people who consumed less iodine than the median. Because these findings are based on post-diagnostic measures, studies with pre-diagnostic dietary iodine are needed for confirmation.

Recreational Physical Activity and Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies.

PURPOSE: Physical activity has been hypothesized to influence cancer occurrence through several mechanisms. To date, its relation with thyroid cancer risk has been examined in relatively few studies. We pooled 2 case-control studies conducted in Cuba and Eastern France to assess the relationship between self-reported practice of recreational physical activity since childhood and thyroid cancer risk. METHODS: This pooled study included 1,008 cases of differentiated thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years in the French and Cuban studies, respectively). Risk factors associated with the practice of recreational physical activity were estimated using OR and 95% CI. Logistic regressions were stratified by age class, country, and gender and were adjusted for ethnic group, level of education, number of pregnancies for women, height, BMI, and smoking status. RESULTS: Overall, the risk of thyroid cancer was slightly reduced among subjects who reported recreational physical activity (OR = 0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more relevant than the duration (years). CONCLUSION: Long-term recreational physical activity, practiced since childhood, may reduce the DTC risk. However, the mechanisms whereby the DTC risk decreases are not yet entirely clear.

Anthropometric Risk Factors for Differentiated Thyroid Cancer in Young Men and Women From Eastern France: A Case-Control Study.

The incidence of thyroid cancer has risen over the past decade, along with a rise in obesity. We studied the role of anthropometric risk factors for differentiated thyroid cancer at the time of diagnosis and at age 20 years in a case-control study conducted in eastern France between 2005 and 2010. The study included 761 adults diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006. They were matched with 825 controls from the general population. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, those with papillary cancer only, and women only. The risk of thyroid cancer was higher for participants with a high body surface area (BSA), great height, or excess weight and for women with a high body fat percentage. Conversely, no significant association was found between body mass index and the risk of thyroid cancer. In the present study, we provide further evidence of the role of BSA and excess weight in the risk of thyroid cancer. These epidemiologic observations should be confirmed by further exploration of the biological mechanisms responsible for the associations of obesity and BSA with thyroid cancer.

Thyroid volume and its relation to anthropometric measures in a healthy cuban population.

OBJECTIVES: The aim of this study was to describe the thyroid volume in healthy adults by ultrasound and to correlate this volume with some anthropometric measures and other differentiated thyroid cancer risk factors. STUDY DESIGN: Thyroid volume and anthropometric measures were recorded in a sample of 100 healthy adults, including 21 men and 79 women aged 18-50 years, living in a non-iodine-deficient area of Havana city. RESULTS: The average thyroid volume was 6.6 ± 0.26 ml; it was higher in men (7.3 ml) than in women (6.4 ml; p = 0.15). In the univariate analysis, thyroid volume was correlated with all anthropometric measures, but in the multivariate analysis, body surface area was found to be the only significant anthropometric parameter. Thyroid volume was also higher in current or former smokers and in persons with blood group AB or B. CONCLUSION: Specific reference values of thyroid volume as a function of body surface area could be used for evaluating thyroid volume in clinical practice. The relation between body surface area and thyroid volume is coherent with what is known about the relation of thyroid volume to thyroid cancer risk, but the same is not true about the relation between thyroid volume and smoking habit.

Common variants at the 9q22.33, 14q13.3 and ATM loci, and risk of differentiated thyroid cancer in the Cuban population.

BACKGROUND: The incidence of differentiated thyroid carcinoma (DTC) in Cuba is low and the contribution of host genetic factors to DTC in this population has not been investigated so far. Our goal was to assess the role of known risk polymorphisms in DTC cases living in Havana. We genotyped five polymorphisms located at the DTC susceptibility loci on chromosome 14q13.3 near NK2 homeobox 1 (NKX2-1), on chromosome 9q22.33 near Forkhead factor E1 (FOXE1) and within the DNA repair gene Ataxia-Telangiectasia Mutated (ATM) in 203 cases and 212 age- and sex- matched controls. Potential interactions between these polymorphisms and other DTC risk factors such as body surface area, body mass index, size, ethnicity, and, for women, the parity were also examined. RESULTS: Significant association with DTC risk was found for rs944289 near NKX2-1 (OR per A allele = 1.6, 95% CI: 1.2-2.1), and three polymorphisms near or within FOXE1, namely rs965513 (OR per A allele = 1.7, 95% CI: 1.2-2.3), rs1867277 in the promoter region of the gene (OR per A allele = 1.5, 95% CI: 1.1-1.9) and the poly-alanine tract expansion polymorphism rs71369530 (OR per Long Allele = 1.8, 95% CI: 1.3-2.5), only the 2 latter remaining significant when correcting for multiple tests. Overall, no association between DTC and the coding SNP D1853N (rs1801516) in ATM (OR per A Allele = 1.1, 95% CI: 0.7-1.7) was seen. Nevertheless women who had 2 or more pregnancies had a 3.5-fold increase in risk of DTC if they carried the A allele (OR 3.5, 95% CI: 3.2-9.8) as compared to 0.8 (OR 0.8, 95% CI: 0.4-1.6) in those who had fewer than 2. CONCLUSIONS: We confirmed in the Cuban population the role of the loci previously associated with DTC susceptibility in European and Japanese populations through genome-wide association studies. Our results on ATM and the number of pregnancies raise interesting questions on the mechanisms by which oestrogens, or other hormones, alter the DNA damage response and DNA repair through the regulation of key effector proteins such as ATM. Due to the small size of our study and to multiple tests, all these results warrant further investigation.